Somatostatin decreases voltage-gated Ca2+ currents in GH3 cells through activation of somatostatin receptor 2

The secretion of growth hormone ( GH) is inhibited by hypothalamic somatostatin ( SRIF) in somatotropes through five subtypes of the somatostatin receptor ( SSTR1 SSTR5). We aimed to characterize the subtype( s) of SSTRs involved in the Ca2+ current reduction in GH3 somatotrope cells using specific SSTR subtype agonists. We used nystatin- perforated patch clamp to record voltage- gated Ca2+ currents, using a holding potential of -80 mV in the presence of K+ and Na+ channel blockers. We first established the presence of T-, L-, N-, and P/ Q- type Ca2+ currents in GH3 cells using a variety of channel blockers ( Ni+, nifedipine, omega- conotoxin GVIA, and omega-agatoxin IVA). SRIF ( 200 nM) reduced Land N- type but not T- or P/ Q- type currents in GH3 cells. A range of concentrations of each specific SSTR agonist was tested on Ca2+ currents to find the maximal effective concentration. Activation of SSTR2 with 10(-7) and 10(-8) M L- 797,976 decreased the voltage- gated Ca2+ current and abolished any further decrease by SRIF. SSTR1, SSTR3, SSTR4, and SSTR5 agonists at 10(-7) M did not modify the voltage- gated Ca2+ current and did not affect the Ca2+ current response to SRIF. These results indicate that SSTR2 is involved mainly in regulating voltage- gated Ca2+ currents by SRIF, which contributes to the decrease in intracellular Ca2+ concentration and GH secretion by SRIF.